scholarly journals 1381. Impact of Total Body Weight on Efficacy of Ceftriaxone in Obese Patients

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S423-S423
Author(s):  
Jamie L Wagner ◽  
J Taylor Loper ◽  
Austin R Morrison ◽  
Kayla R Stover ◽  
Katie E Barber
Keyword(s):  
Treatment Failure ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Source Control ◽  
Causative Organism ◽  
Obese Patients ◽  
Discharge Disposition ◽  
Single Temperature ◽  
Total Body ◽  
Nonobese Patients

Abstract Background Ceftriaxone (CRO), while highly protein bound, retains a small volume of distribution. Obese patients have larger volumes of distributions and higher clearance than nonobese patients. The effect of these differences on the pharmacokinetics and efficacy of CRO remain unclear. Methods This retrospective cohort study included adult in-patients who received CRO for ≥72 hours as definitive monotherapy from July 2015 to July 2017. Patients were excluded if there was a lack of adequate source control at 72 hours or if there was a polymicrobial infection requiring multiple antibiotics. Obesity was defined as BMI ≥30 kg/m2. The primary outcome was clinical treatment failure, defined as changing therapy at >72 hours due to clinical worsening, leukocytosis (WBC > 10 × 109/L), fever (single temperature >100.9°F) for >72 hours, or readmission to the hospital within 30 days for re-infection. Secondary outcomes included discharge disposition and 30-day readmission. Results One hundred one patients were included: 39 obese patients and 62 nonobese patients. Median [IQR] age was 62 [51–70] years; 55% males. Median weight was 103 [95–120] kg in obese patients vs. 66 [58–77] kg in nonobese patients (P < 0.001). There were no differences in comorbidities (Charlson 3[1–5] obese vs. 2[1–4] nonobese; P = 0.293). Infection sources were similar: urinary tract (54% obese vs. 52% nonobese; P = 0.827), respiratory (28% obese vs. 23% nonobese; P = 0.524), bloodstream (20% obese vs. 23% nonobese; P = 0.806). The most common causative organism was E. coli (48%). There were no differences in CRO regimen between groups (1g q24h: obese 54% vs. nonobese 69%; P = 0.115). Treatment failure occurred in 24 (61%) obese patients compared with 25(40%) nonobese patients (P = 0.038). Obese patients had delayed resolution of leukocytosis (54% vs. 29%, P = 0.013). Eight patients died (13% obese vs. 5% nonobese; P = 0.255); 82% of patients were not readmitted within 30 days. Conclusion Obese patients treated with ceftriaxone had higher rates of treatment failure compared with nonobese patients. While not statistically significant, there was numerically higher mortality in obese patients compared with nonobese patients. Obese patients may be slow to recover from infection when treated with CRO. Disclosures All authors: No reported disclosures.

scholarly journals Pharmacokinetics of Intravenous Linezolid in Moderately to Morbidly Obese Adults

2012 ◽  
Vol 57 (3) ◽  
pp. 1144-1149 ◽  
Author(s):  
Amira A. Bhalodi ◽  
Pavlos K. Papasavas ◽  
Darren S. Tishler ◽  
David P. Nicolau ◽  
Joseph L. Kuti
Keyword(s):  
Body Weight ◽  
Ideal Body Weight ◽  
Total Body Weight ◽  
Compartment Model ◽  
Central Compartment ◽  
Volume Of Distribution ◽  
Lean Body Weight ◽  
Morbidly Obese ◽  
Total Body ◽  
Nonobese Patients

ABSTRACTThe pharmacokinetics of linezolid was assessed in 20 adult volunteers with body mass indices (BMI) of 30 to 54.9 kg/m2receiving 5 intravenous doses of 600 mg every 12 h. Pharmacokinetic analyses were conducted using compartmental and noncompartmental methods. The mean (±standard deviation) age, height, and weight were 42.2 ± 12.2 years, 64.8 ± 3.5 in, and 109.5 ± 18.2 kg (range, 78.2 to 143.1 kg), respectively. Linezolid pharmacokinetics in this population were best described by a 2-compartment model with nonlinear clearance (original value, 7.6 ± 1.9 liters/h), which could be inhibited to 85.5% ± 12.2% of its original value depending on the concentration in an empirical inhibition compartment, the volume of the central compartment (24.4 ± 9.6 liters), and the intercompartment transfer constants (K12andK21) of 8.04 ± 6.22 and 7.99 ± 5.46 h−1, respectively. The areas under the curve for the 12-h dosing interval (AUCτ) were similar between moderately obese and morbidly obese groups: 130.3 ± 60.1 versus 109.2 ± 25.5 μg · h/ml (P= 0.32), and there was no significant relationship between the AUC or clearance and any body size descriptors. A significant positive relationship was observed for the total volume of distribution with total body weight (r2= 0.524), adjusted body weight (r2= 0.587), lean body weight (r2= 0.495), and ideal body weight (r2= 0.398), but not with BMI (r2= 0.171). Linezolid exposure in these obese participants was similar overall to that of nonobese patients, implying that dosage adjustments based on BMI alone are not required, and standard doses for patients with body weights up to approximately 150 kg should provide AUCτ values similar to those seen in nonobese participants.

Theophylline Clearance in Obese Patients in Relation to Smoking and Congestive Heart Failure

1983 ◽  
Vol 17 (4) ◽  
pp. 274-276 ◽  
Author(s):  
Richard L. Slaughter ◽  
Robert A. Lanc
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Body Weight ◽  
Ideal Body Weight ◽  
Total Body Weight ◽  
Obese Patients ◽  
Ideal Body ◽  
Total Body ◽  
Nonobese Patients ◽  
Body Clearance

The effect of obesity on the total body clearance (Cltot) of theophylline was evaluated in nonsmokers and smokers with and without congestive heart failure (CHF). The obese patients were compared with similar nonobese subjects with regard to age, sex, and disease state. The total patient population numbered 150 adults. Cltot of theophylline, based on total body weight (TBW), averaged 0.60 ± 0.20 ml/min/kg in obese nonsmokers and did not differ from the nonobese, nonsmoking group. In obese nonsmoking patients with CHF, Cltot based on TBW was 0.40 ± 0.14 ml/min/kg, which was similar to Cltot values in nonsmoking CHF patients who were not obese. A trend toward a reduction in Cltot, based on TBW, as TBW increased, in nonsmoking patients with and without CHF, was observed. In contrast to the Cltot in nonsmokers, the Cltot of theophylline in obese smokers with and without CHF was similar to the Cltot values in nonobese populations only when based on ideal body weight. However, when compared with nonsmoking, nonobese patients, no differences were observed when Cltot was corrected for TBW. These findings suggest that theophylline maintenance dose can be based on TBW in obese patients who are smokers and nonsmokers (with and without CHF), using the average Cltot obtained for the nonsmoking patients with and without CHF.

scholarly journals Effect of Obesity on Clinical Failure of Patients Treated with Beta-Lactams

2021 ◽  
Author(s):  
Nathan A Pinner ◽  
Natalie G Tapley ◽  
Katie E Barber ◽  
Kayla R Stover ◽  
Jamie L Wagner
Keyword(s):  
Treatment Failure ◽  
Clinical Outcomes ◽  
Hospital Length Of Stay ◽  
Source Control ◽  
Definitive Treatment ◽  
Therapeutic Drug ◽  
Obese Patients ◽  
Definitive Therapy ◽  
All Cause Mortality ◽  
The Impact

Abstract Background Altered pharmacokinetics in obese patients raise concerns over worse clinical outcomes. This study assessed whether obese patients receiving a beta-lactam (BL) have worse clinical outcomes compared to non-obese patients and to identify if therapeutic drug monitoring (TDM) may be beneficial. Methods This multi-center, retrospective cohort included hospitalized adults admitted from July 2015-July 2017 treated with a BL as definitive monotherapy against a Gram-negative bacilli for ≥72 hours. Patients were excluded if there was lack of source control or if polymicrobial infections required >1 antibiotic for definitive therapy. Patients were classified based on body mass index (BMI): non-obese (BMI ≤29.9 kg/m 2) and obese (BMI ≥30.0 kg/m 2). The primary outcome was clinical treatment failure, and secondary were hospital length of stay (LOS), inpatient all-cause mortality, and 30-day all-cause readmission. Results There were 257 (43.6%) obese patients and 332 (56.4%) non-obese patients included. The most common infections were urinary (50.9%) and respiratory (31.4%). Definitive treatment was driven by 3 rd generation cephalosporins (46.9%) and cefepime (44.7%). Treatment failure occurred in 131 (51%) obese patients and 109 (32.8%) non-obese patients (p<0.001). Obesity and respiratory source were independently associated with increased likelihood of treatment failure. Obese patients were hospitalized longer than non-obese patients (p=0.002), but no differences were found for all-cause mortality (p=0.117) or infection-related readmission (0=0.112). Conclusions Obese patients treated with BLs have higher rates of treatment failure and longer hospitalization periods than non-obese patients. Future studies are needed to assess the impact of TDM and specific dosing recommendations for targeted infection types.

scholarly journals Comparable Population Pharmacokinetics and Pharmacodynamic Breakpoints of Cefpirome in Cystic Fibrosis Patients and Healthy Volunteers

2011 ◽  
Vol 55 (6) ◽  
pp. 2927-2936 ◽  
Author(s):  
J. B. Bulitta ◽  
M. Kinzig ◽  
C. B. Landersdorfer ◽  
U. Holzgrabe ◽  
U. Stephan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Healthy Volunteers ◽  
High Performance ◽  
Standard Dose ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Nonparametric Bootstrap ◽  
Population Pk ◽  
Total Body ◽  
Similar Body

ABSTRACTCystic fibrosis (CF) patients are often reported to have higher clearances and larger volumes of distribution per kilogram of total body weight (WT) for beta-lactams than healthy volunteers. As pharmacokinetic (PK) data on cefpirome from studies of CF patients are lacking, we systematically compared its population PK and pharmacodynamic breakpoints for CF patients and healthy volunteers of similar body size. Twelve adult CF patients (median lean body mass [LBM] = 45.7 kg) and 12 healthy volunteers (LBM = 50.0 kg) received a single 10-min intravenous infusion of 2 g cefpirome. Plasma and urine concentrations were determined by high-performance liquid chromatography (HPLC). Population PK and Monte Carlo simulations were performed using NONMEM and S-ADAPT and a duration of an unbound plasma concentration above the MIC ≥ 65% of the dosing interval as a pharmacodynamic target. Unscaled clearances for CF patients were similar to those seen with healthy volunteers, and the volume of distribution was 6% lower for CF patients. Linear scaling of total clearance by WT resulted in clearance that was 20% higher (P≤ 0.001 [nonparametric bootstrap]) in CF patients. Allometric scaling by LBM explained the differences between the two subject groups with respect to average clearance and volume of distribution and reduced the unexplained between-subject variability of renal and nonrenal clearance by 10 to 14%. For the CF patients, robust (>90%) probabilities of target attainment (PTA) were achieved by the administration of a standard dose of 2 g/70 kg WT every 12 h (Q12h) given as 30-min infusions for MICs ≤ 1.5 mg/liter. As alternative dosage regimens, a 5-h infusion of 1.33 g/70 kg WT Q8h achieved robust PTAs for MICs ≤ 8 to 12 mg/liter and a continuous infusion of 4 g/day for MICs ≤ 12 mg/liter. Prolonged infusion of cefpirome is expected to be superior to short-term infusions for MICs between 2 and 12 mg/liter.

Vancomycin volume of distribution estimation in adults with class III obesity

2019 ◽  
Author(s):  
Ryan D Dunn ◽  
Ryan L Crass ◽  
Joseph Hong ◽  
Manjunath P Pai ◽  
Lynne C Krop
Keyword(s):  
Body Weight ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Patient Specific ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Parameter Estimates ◽  
Class Iii ◽  
Class Iii Obesity ◽  
Total Body

Abstract Purpose To compare methods of estimating vancomycin volume of distribution (V) in adults with class III obesity. Methods A retrospective, multicenter pharmacokinetic analysis of adults treated with vancomycin and monitored through measurement of peak and trough concentrations was performed. Individual pharmacokinetic parameter estimates were obtained via maximum a posteriori Bayesian analysis. The relationship between V and body weight was assessed using linear regression. Mean bias and root-mean-square error (RMSE) were calculated to assess the precision of multiple methods of estimating V. Results Of 241 patients included in the study sample, 159 (66.0%) had a BMI of 40.0–49.9 kg/m2, and 82 (34.0%) had a BMI of ≥50.0 kg/m2. The median (5th, 95th percentile) weight of patients was 136 (103, 204) kg, and baseline characteristics were similar between BMI groups. The mean ± S.D. V was lower in patients with a BMI of 40.0–49.9 kg/m2 than in those with a BMI of ≥50.0 kg/m2 (72.4 ± 19.6 L versus 79.3 ± 20.6 L, p = 0.009); however, body size poorly predicted V in regression analyses (R2 < 0.20). A fixed estimate of V (75 L) or use of 0.52 L/kg by total body weight yielded similar bias and error in this population. Conclusion Results of the largest analysis of vancomycin V in class III obesity to date indicated that use of a fixed V value (75 L) and use of a TBW-based estimate (0.52 L/kg) for estimation of vancomycin V in patients with a BMI of ≥40.0 kg/m2 have similar bias. Two postdistribution vancomycin concentrations are needed to accurately determine patient-specific pharmacokinetic parameters, estimate AUC, and improve the precision of vancomycin dosing in this patient population.

P0264ASSESSMENT OF GFR IN MORBIDLY OBESE PATIENTS USING DIFFERENT EQUATIONS: WHICH IS THE BEST?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Alaa Sabry ◽  
Amir Basiony ◽  
Mohamed Kamal
Keyword(s):  
Body Weight ◽  
Creatinine Clearance ◽  
Glomerular Filtration ◽  
Total Body Weight ◽  
Lean Body Weight ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Morbidly Obese Patient ◽  
Gault Formula ◽  
Total Body

Abstract Background and Aims Obesity is a potent risk factor for the development of kidney disease. The prevalence of abdominal obesity in Egyptians based upon the European cut-off points was 30.2% for men and 70.9% for women. To detect the best formula for estimation of glomerular filtration rates in morbidly obese individuals. Method: In this prospective study 82 morbidly obese patients were included, Age: 15 to 65 years, Morbidly obese patient (BMI &gt; 40 Kg/m2), Creatinine clearance calculated from a 24-h urine was done, Estimated glomerular filtration rate (eGFR): It was assessed to be correlated with creatinine clearance and detect the most suitable formula for morbidly obese patients. Cockcroft-Gault formula:  Cockcroft-Gault formula (for total body weight): ockcroft-Gault formula (for adjusted body weight): Cockcroft-Gault formula (for lean body weight), MDRD-eGFR (Modification of Diet in Renal Disease equation) (Shahbaz & Gupta, 2019), CKD-epidemiology (CKD-EPI): (Levey, et al, 2009) Results Demogrphic criteria of the studdied patients Conclusion: The equations that had the nearest values to creatinine clearance were CG-TBW-GFR and CGAjBW- GFR, both of them had a moderate reliability with more agreement for the CG-TBW-GFR equation . The CG-TBW-GFR formula was the most reliable one to measure GFR, followed by the CG-AjBW-GFR formula, while the CG-IBW, CG-LBW, MDRD-GFR and CKD-EPI-GFR formulae were not reliable at all .

scholarly journals Suture pattern does not influence outcomes of endoscopic sleeve gastroplasty in obese patients

2020 ◽  
Vol 08 (10) ◽  
pp. E1349-E1358
Author(s):  
E. Espinet-Coll ◽  
J. Nebreda-Durán ◽  
M. Galvao-Neto ◽  
C. Bautista-Altamirano ◽  
P. Diaz-Galán ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight Loss ◽  
Total Body Weight ◽  
Obese Patients ◽  
Serious Adverse Events ◽  
Comparative Review ◽  
Sleeve Gastroplasty ◽  
Total Body ◽  
Suture Patterns ◽  
Comorbidity Resolution

Abstract Background and study aims ESG is an effective and safe medium-term procedure for obesity treatment. A variety of suture patterns have been reported. We aimed to compare whether there are differences in efficacy depending on suture pattern used. Patients and methods Retrospective and comparative review of 5 years of prospectively collected data, including consecutive obese patients undergoing ESG at two collaborative centers. Primary outcomes included weight loss (mainly % total body weight loss [TBWL] and % exces weight loss [EWL]) at 12 months and safety profile. We compared them according to three suture patterns (transverse bilinear [TBp], longitudinal [Lp] and transverse monolinear [TMp]), and number of sutures (4 – 7) and stitches (< 25, 25 to 30 and > 30) applied. Evolution of major obesity-associated morbidities (hypertension, dyslipidemia, Type 2 diabetes mellitus (T2DM), sleep obstructive apnea syndrome, and arthropathy) were also described. Results 88 patients (mean age 46.1±12.3 years, 69.3 % female) underwent ESG. Mean body mass index (BMI) at baseline was 39.40 ± 4.69 kg/m². At 1 year, %TBWL was 17.36 ± 6.09 % (%EWL 46.41±20.6 %) with TBWL > 10 % in 95.5 % of patients (EWL > 25 % in 94.3 % of patients). According to pattern, there were no differences in %TBWL but there were in %EWL (43.7 ± 20.4 %, 59.8 ± 18.9 % and 45.4 ± 14.9 % in TBp, Lp and TMp patterns, respectively) (P = 0.034). No differences were found related to number of sutures (mean 5.2 ± 0.73, r = 4 – 7) or stitches (mean 27.4 ± 6.50, r = 18 – 50) applied. Forty-three of 72 (59.7 %) major comorbidities were resolved. No serious adverse events were observed with any pattern. Conclusions ESG is an effective procedure at 12-month follow-up for weight loss and comorbidity resolution. All three analyzed patterns are safe and effective without differences in %TBWL, but there was a slight increase in %EWL in Lp, regardless of the number of sutures or stitches applied.

scholarly journals Impact of Obesity on Ceftriaxone Efficacy

Diseases ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 27
Author(s):  
Katie E. Barber ◽  
J. Taylor Loper ◽  
Austin R. Morrison ◽  
Kayla R. Stover ◽  
Jamie L. Wagner
Keyword(s):  
Treatment Initiation ◽  
Source Control ◽  
Obese Patients ◽  
Clinical Failure ◽  
Klebsiella Species ◽  
Single Temperature ◽  
Definitive Therapy ◽  
Dosing Regimens ◽  
Standard Set ◽  
Clinical Worsening

Background: Ceftriaxone has standard, set dosing regimens that may not achieve adequate serum concentrations in obese patients compared to non-obese patients. The purpose of this study was to evaluate the effect of obesity on ceftriaxone efficacy when used as definitive monotherapy to treat infections. Methods: This retrospective cohort included adult inpatients treated with ceftriaxone monotherapy for ≥72 h between July 01, 2015–July 31, 2017. Patients were excluded if their infection lacked source control within 72 h or if they had polymicrobial infections requiring more than one antibiotic for definitive therapy. The primary outcome was the rate of clinical failure between obese versus non-obese patients, defined as a composite of (1) change in definitive therapy > 72 h due to clinical worsening; (2) residual leukocytosis (white blood cell count (WBC) > 10 × 109/L) > 72 h after treatment initiation; (3) presence of a fever (single temperature > 100.9 °F) > 72 h after treatment initiation; or (4) readmission within 30 days due to re-infection with the same organism. Results: A total of 101 patients were included in the study: 39 obese and 62 non-obese. The most common indications for ceftriaxone were urinary tract (52.5%), respiratory tract (24.8%), and bloodstream (24.8%) infections. The most commonly isolated organisms were Escherichia coli (48.5%) and Klebsiella species (15.8%). Most patients received 1g every 24 h. Clinical failure was observed in 61.5% of obese patients versus 40.3% of non-obese patients (p = 0.038). Conclusion: Obese patients treated with ceftriaxone were more likely to experience clinical failure when compared to non-obese patients. Further analyses are warranted to determine if weight-based dosing is required in obese patients treated with ceftriaxone.

Estimation of Total Body Weight in Obese Patients

2009 ◽  
Vol 28 (3) ◽  
pp. 139-145 ◽  
Author(s):  
Cameron S. Crandall ◽  
Stephanie Gardner ◽  
Darren A. Braude
Keyword(s):  
Body Weight ◽  
Total Body Weight ◽  
Obese Patients ◽  
Total Body
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